A matching algorithm for catalytic residue site selection in computational enzyme design
A matching algorithm for catalytic residue site selection in computational enzyme design
复制标题
计算酶设计中催化残基位点选择的匹配算法
DOI：
10.1002/pro.685
复制
发表时间：
2011-09-01
期刊：
影响因子：
8
通讯作者：
Zhu, Yushan
中科院分区：
文献类型：
--
作者：
Lei, Yulin;Luo, Wenjia;Zhu, Yushan
开发了一种基于环闭合的顺序算法PRODA_MATCH，用于将催化残基匹配到支架上，以进行计算机模拟酶设计。该算法的计算复杂度是关于活性中心数、催化残基数和循环坐标下降步的最大迭代次数的多项式。该匹配算法独立于旋转异构体库，该旋转异构体库使得催化残基能够在反应坐标期间采取任何所需的构象。通过优化过渡态官能团与催化残基之间的催化几何参数，确定过渡态的准确位置。在残基的周围引入伪球，使得算法在匹配过程中就考虑到了约束。本机催化残基网站的重述被用作基准来评估新的算法。测试集的计算结果表明，天然催化残留物位点被成功识别，并在10个化学反应中的7个的前10个设计中排名。这表明，匹配算法有可能被用于设计工业酶所需的反应。
A loop closure-based sequential algorithm, PRODA_MATCH, was developed to match catalytic residues onto a scaffold for enzyme design in silico. The computational complexity of this algorithm is polynomial with respect to the number of active sites, the number of catalytic residues, and the maximal iteration number of cyclic coordinate descent steps. This matching algorithm is independent of a rotamer library that enables the catalytic residue to take any required conformation during the reaction coordinate. The catalytic geometric parameters defined between functional groups of transition state (TS) and the catalytic residues are continuously optimized to identify the accurate position of the TS. Pseudo-spheres are introduced for surrounding residues, which make the algorithm take binding into account as early as during the matching process. Recapitulation of native catalytic residue sites was used as a benchmark to evaluate the novel algorithm. The calculation results for the test set show that the native catalytic residue sites were successfully identified and ranked within the top 10 designs for 7 of the 10 chemical reactions. This indicates that the matching algorithm has the potential to be used for designing industrial enzymes for desired reactions.